Cédric Blanpain

Cédric Blanpain (born 6 September 1970) is a Belgian researcher in the field of stem cells (embryology, tissue homeostasis and cancer). He is a tenured professor of developmental biology and genetics at Université Libre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine. He was one of the first researchers in the world to use cell lineage tracing in cancer research and he showed for the first time the existence of cancer stem cells in solid tumors in vivo. He was selected by Nature as one of 10 People who mattered most in 2012 and he received the outstanding young investigator award of the International Society for Stem Cell Research.

Cédric Blanpain
Born(1970-09-06)6 September 1970
Uccle, Belgium
Alma materUniversité libre de Bruxelles (MD/PhD)
Awards
Outstanding Young Investigator Award ISSCR

Prix Quinquennal FNRS

Scientific career
Fields
Institutions

Biography

Born in Uccle in 1970.,[1] Cedric Blanpain attended Collège Saint-Hubert for his secondary education. Graduating in 1987, he started medical school with an aim of becoming a psychiatrist.[2] As soon as his first year, he started doing research in human physiology at the Institut de Recherche Inter-Disciplinaire en Biologie Moléculaire and was thereafter introduced to molecular biology by Gilbert Vassart, the director of the IRIBHM.[2]

After graduating summa cum laude from medical school in 1995, Cedric Blanpain started a specialization in internal medicine. In the third year, he interrupted his clinical education to focus on research. He did his PhD in the lab of Marc Parmentier, dedicated to the study of G-protein coupled receptors. During this period, the Parmentier lab characterized the CCR5 GPCR and discovered its role as a co-receptor in HIV infection.[3] Cedric Blanpain earned his PhD in 2001 for his work on CCR5 and HIV infection and received the 2002 Galen Award of Pharmacology in recognition of his graduate work.[4]

After earning his PhD, Cedric Blanpain went back to finish his board certification in internal medicine, sub-specializing in genetics. From there on, his career would be entirely dedicated to research.[1] In 2002, he earned a fellowship from the Belgian American Educational Foundation to study in the USA.[5] He did his post-doc with Elaine Fuchs (a lifelong mentor[6]) at the Laboratory of Mammalian Cell Biology and Development of Rockefeller University, studying epidermal stem cells and tissue differentiation.[7] The Fuchs lab was one of the few labs then studying epidermal stem cells.[3] He was also a long-term fellow of NATO and the Human Frontier Science Program[8] during this period.

In 2006, he accepted an offer from the Belgian National Research Fund to become an independent group leader at his home institute, the IRIBHM.[9] He established the stem cells and cancer lab at ULB, becoming professor in 2013. He received a starting grant from the ERC in 2008 and a consolidator grant in 2014. He received a career development award from the Human Frontier Science Program.[8] Since 2011, he is also an investigator of the Walloon Excellence in Life Science and Biotechnology (WELBIO).[1] He pioneered the use of lineage tracing in cancer research.[10] Ever since establishing his lab, Blanpain received several international awards, including the EMBO Young Investigator Award[11] and the Liliane Bettencourt Award for Life Sciences 2012.[12]

He has also written several authoritative reviews on stem cells for journals such as Cell,[13] Science,[14][15] Cell Stem Cell[16][17][18] and Nature.[19][20]

Research

Cancer cell of origin, tumor stem cells and heterogeneity

The Blanpain lab has been studying the cells at the origin of epithelial tumors as well as the role and the mechanisms by which cancer stem cells regulate tumor growth and relapse after therapy.[21][22]

His lab showed that basal cell carcinoma stem from cells of the interfollicular epidermis and infundibulum rather than hair follicles.[23] In 2018, his lab identified the cell population in basal cell carcinoma that mediates vismodegib resistance. They also showed that the administration of Vismodegib in combination with a Wnt inhibitor leads to tumor eradication, a potential new strategy against BCC.[24]

They defined for the first time the quantitative dynamics of tumor initiation at the single cell level from the activation of the oncogene to the development of invasive tumors and demonstrated that the capacity of oncogene expressing cells to induce tumor formation depends on the specific clonal dynamics of the oncogene targeted stem cells at the origin of the cancer.[25]

The Blanpain lab has been studying the different cell states of the epithelio-mesenchymental transition that invasive tumor undergo: they demonstrated that different epidermal stem cells are responsible for invasive squamous cell carcinoma, that hair follicle lineage is primed to undergo EMT during tumorigenesis.[26] They characterized the different transitional states of tumor cells during EMT, in particular they showed that specific subpopulations have higher potential to undergo EMT and metastasize. By screening a large panel of cell surface markers, Blanpain and colleagues identified the existence of different tumor subpopulations in skin and mammary primary tumors associated with different stages of EMT from epithelial to completely mesenchymal states passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumor propagating cell capacity, they displayed different cellular plasticity, invasive and metastatic potential.[27]

The lab also showed the role of PIK3CA in inducing heterogeneity in breast tumors, especially its role in reprogramming basal cells into luminal ones and vice versa. They showed that cell fate reprograming during tumorigenesis correlated with the cell of origin, tumor type and different clinical outcomes of breast tumors.[28]

His team showed the first experimental evidence for the existence of cancer stem cells during unperturbed solid tumor growth in vivo.[29] They also showed the role of VEGF in regulating cancer stem cells.[30]

In squamous cell carcinoma, his group also identified a novel population of cancer stem cells in skin cancers expressing Sox2, they demonstrated by lineage ablation that Sox2 cancer stem cells are essential for tumor initiation and progression in primary tumors and identified the gene network regulated by Sox2 in primary tumour cells in vivo as well as several direct Sox2 target genes controlling critical tumor functions.[31] They also demonstrated the role of the Twist1 gene in cancer for tumor maintenance and growth, within squamous cell carcinoma again.[32]

Breast Gland Development

Using lineage tracing of basal cells and luminary mammary gland cells during embryonic development and post-natal development, the Blanpain lab showed that different mammary tissue lineages stem from multipotent embryonic progenitors. These multipotent progenitors are replaced soon after birth by unipotent stem cells.[33] His group developed new techniques to perform quantitative lineage tracing to unravel the multilineage differentiation potential of stem cells during development and adult homeostasis. Using novel lineage tracing strategies, they demonstrated that ER positive cells in the mammary gland developed and are maintained in adult gland through unipotent progenitors that are restricted to hormone receptor expressing cells.[34] The differentiation of the multipotent progenitors into basal cells is mediated through p63 activation. Finally, these multipotent progenitors express similar genes as breast tissue tumors (e.g. Sox11, Stmn1 and Mdk), showing that reactivation of multipotency is involved in tumorigenesis.[35]

Epithelial stem cells

After he started work at the Fuchs lab, Blanpain was part of a world-first: isolating stem cells based on their quiescence using histone H2B-fluorescent protein.[36] The paper, cited more than 1900 times, has been seminal in subsequent work on stem cells.[3] Using monoclonal antibodies, Blanpain managed to isolate hair follicle bulge stem cells and demonstrated their multi-potency (the fact that a single bulge stem cell can differentiate into all epidermal cell lineages). He also transplanted these mouse HF stem cells through grafts, leading to hair growth.[37] Furthermore, he co-authored several papers characterizing the role of Wnt/Beta-Catenin stabilization in precocious bulge stem cell activation[38] and the role of Notch signaling pathway in promoting spine cell development.[39]

CCR5 and HIV

Cedric Blanpain started his research career working on the CCR5 co-receptor which had been characterized by the Parmentier lab. He worked on understanding the function of the receptor and how the HIV interacts with it. The young researcher showed that endocytosis of the HIV is essential to the cell's infection.[40] He was able to find the first chemokine antagonist to the receptor[41] as well as antibodies that could mediate the oligomerization of the receptor.[42] He also studied the Delta32 inactivating allele of CCR5 which prevents HIV infection[43]

Awards and honors
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References
  1. "Itinéraire d'un chercheur gâté" (PDF). Esprit Libre. February–March 2012.
  2. Béatrice Delvaux and Marie Thieffry. "Entretien avec Cédric Blanpain" (11 and 12 August 2018). Le Soir.
  3. Scudellari, Megan (July 2013). "Master of Fate". The Scientist.
  4. "Galen Prize of Pharmacology Laureates". Galen Prize.
  5. "BAEF Alumni 2002". BAEF.
  6. Fuchs, Elaine (14 June 2012). "Cédric Blanpain: ISSCR's Outstanding Young Investigator for 2012". Cell Stem Cell. 10 (6): 751–752. doi:10.1016/j.stem.2012.05.001.
  7. "Cedric Blanpain, un chercheur qui trouve plus vite que son ombre". L'Echo. 30 November 2015.
  8. "Cedric Blanpain". HFSP. Archived from the original on 2019-04-01. Retrieved 2019-03-25.
  9. "Prix Quinquennaux" (PDF). FNRS.
  10. Baker, Monya (19 December 2012). "366 days: Nature's 10. Ten people who mattered this year". Nature.
  11. "Cedric Blanpain: an insatiable curiosity". EMBO Encounters.
  12. "Prix Liliane Bettencourt pour les Sciences du Vivant". Fondation Bettencourt Schueller. October 2014.
  13. Blanpain, C., Horsley, V. & Fuchs, E (2007). "Epithelial stem cells: turning over new leaves". Cell. 128 (3): 445–458. doi:10.1016/j.cell.2007.01.014. PMC 2408375. PMID 17289566.CS1 maint: multiple names: authors list (link)
  14. Blanpain, C. & Fuchs, E. "Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration". Science. 344.CS1 maint: multiple names: authors list (link)
  15. Boumahdi, S. & Blanpain (2016). "Tracking the origins of tumorigenesis". Science. 351 (6272): 453–454. Bibcode:2016Sci...351..453B. doi:10.1126/science.aad9670. PMID 26823415.
  16. Driessens, G. & Blanpain, C (2011). "Long live sox2: sox2 lasts a lifetime". Cell Stem Cell. 9 (4): 283–284. doi:10.1016/j.stem.2011.09.007. PMID 21982223.CS1 maint: multiple names: authors list (link)
  17. Blanpain, C. & Sotiropoulou, P. A. (2010). "dominant role of the hair follicle stem cell niche in regulating melanocyte stemness". Cell Stem Cell. 6 (2): 95–96. doi:10.1016/j.stem.2010.01.006. PMID 20144781.CS1 maint: multiple names: authors list (link)
  18. Blanpain C (2019). "Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance". Cell Stem Cell. 24 (1): 65–78. doi:10.1016/j.stem.2018.11.011. PMID 30554963.
  19. Blanpain, C (2010). "Stem cells: Skin regeneration and repair". Nature. 464 (7289): 686–687. Bibcode:2010Natur.464..686B. doi:10.1038/464686a. PMID 20360726.
  20. Aragona, M. & Blanpain (2017). "Gene therapy: Transgenic stem cells replace skin". Nature. 551 (7680): 306–307. Bibcode:2017Natur.551..306A. doi:10.1038/nature24753. PMID 29132145.
  21. Lambert, Philippe (2 February 2017). "Cédric Blanpain, chercheur pure souche". Journal du Médecin.
  22. Sedwick, Caitlin. "Cédric Blanpain: The stories stem cells tell". 199 (4). Journal Cell Biology.
  23. Youssef, K (2010). "Identification of the cell lineage at the origin of basal cell carcinoma". Nature Cell Biology. 12 (3): 299–305. doi:10.1038/ncb2031. PMID 20154679.
  24. Sánchez-Danés, A (2018). "A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy". Nature. 562 (7727): 434–438. Bibcode:2018Natur.562..434S. doi:10.1038/s41586-018-0603-3. PMC 6295195. PMID 30297799.
  25. Sanchez-Danes, A (2016). "Defining the clonal dynamics leading to mouse skin tumour initiation". Nature. 596 (7616): 298–303. Bibcode:2016Natur.536..298S. doi:10.1038/nature19069. PMC 5068560. PMID 27459053.
  26. Latil, A (2017). "Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition". Cell Stem Cell. 20 (2): 191–204. doi:10.1016/j.stem.2016.10.018. PMC 5939571. PMID 27889319.
  27. Pastushenko, I (2018). "Identification of the tumour transition states occurring during EMT". Nature. 556 (7702): 463–468. Bibcode:2018Natur.556..463P. doi:10.1038/s41586-018-0040-3. PMID 29670281.
  28. Van Keymeulen, A (2015). "Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity". Nature. 525 (7567): 119–123. Bibcode:2015Natur.525..119V. doi:10.1038/nature14665. PMID 26266985.
  29. Driessens, G (2012). "Defining the mode of tumour growth by clonal analysis". Nature. 488 (7412): 527–530. Bibcode:2012Natur.488..527D. doi:10.1038/nature11344. PMC 5553110. PMID 22854777.
  30. Beck, B (2011). "A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours". Nature. 478 (399–403): 399–403. Bibcode:2011Natur.478..399B. doi:10.1038/nature10525. PMID 22012397.
  31. Boumahdi, A (2014). "SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma". Nature. 511 (7508): 246–250. Bibcode:2014Natur.511..246B. doi:10.1038/nature13305. PMID 24909994.
  32. Beck, B (2015). "Different levels of twist1 regulate skin tumor initiation, stemness, and progression". Cell Stem Cell. 16 (1): 67–79. doi:10.1016/j.stem.2014.12.002. PMID 25575080.
  33. Van Keymeulen, A (2011). "Distinct stem cells contribute to mammary gland development and maintenance". Nature. 479 (7372): 189–193. Bibcode:2011Natur.479..189V. doi:10.1038/nature10573. PMID 21983963.
  34. Van Keymeulen, A (2017). "Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage". Cell Reports. 20 (7): 1525–1532. doi:10.1016/j.celrep.2017.07.066. PMC 5575359. PMID 28813665.
  35. Wuidart, A (2018). "Early lineage segregation of multipotent embryonic mammary gland progenitors". Nature Cell Biology. 20 (6): 666–676. doi:10.1038/s41556-018-0095-2. PMC 5985933. PMID 29784918.
  36. Tumbar, T (2004). "Defining the epithelial stem cell niche in skin". Science. 303 (5656): 359–363. Bibcode:2004Sci...303..359T. doi:10.1126/science.1092436. PMC 2405920. PMID 14671312.
  37. Blanpain, C (2004). "Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche". Cell. 118 (5): 635–648. doi:10.1016/j.cell.2004.08.012. PMID 15339667.
  38. Lowry, WE (2005). "Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells". Genes & Development. 19 (13): 1596–1611. doi:10.1101/gad.1324905. PMC 1172065. PMID 15961525.
  39. Blanpain, C. "Canonical notch signaling functions as a commitment switch in the epidermal lineage". Genes & Development. 20 (3022–3035).
  40. Blanpain, C (2002). "CCR5 and HIV infection". Receptors and Channels. 8 (1): 19–31. doi:10.1080/10606820212135.
  41. Blanpain, C (1999). "CCR5 Binds Multiple CC-Chemokines: MCP-3 Acts as a Natural Antagonist". Blood. 94 (6): 1899–1905. doi:10.1182/blood.V94.6.1899.
  42. Blanpain, C (2002). "Multiple active states and oligomerization of CCR5 revealed by the functional properties of monoclonal antibodies". Molecular Biology of the Cell. 13 (2): 723–737. doi:10.1091/mbc.01-03-0129. PMC 65662. PMID 11854425.
  43. Blanpain, C (2000). "Multiple nonfunctional alleles of CCR5 are frequent in various human populations". Blood. 96 (5): 1638–1645. doi:10.1182/blood.V96.5.1638.
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  48. "Chaire Bauchau". AdrienBauchau.
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